Published in Headache on October 3, 2025
Link: https://doi.org/10.1111/head.15066

Abstract:
Cluster headache (CH) is a disabling primary headache disorder with limited therapeutic options. Calcitonin gene-related peptide (CGRP) is known to be involved in CH pathophysiology; however, except for galcanezumab (300 mg) in episodic CH, anti-CGRP monoclonal antibodies did not reduce CH attacks in randomized clinical trials. Atogepant is an oral, small-molecule, CGRP receptor antagonist, which is approved for the preventive treatment of migraine. Here, we describe four case reports of CH (two episodic CH and two chronic CH), unresponsive to previous prophylactic treatments, who responded to daily atogepant (60 mg). Chronic CH cases were refractory to subcutaneous galcanezumab. In one case, a reduction to atogepant (30 mg daily) resulted in recurrence of headache attacks, which subsided on reintroduction of the initial dose. No serious adverse effects were reported. Despite the limited number of cases and the open retrospective design, our case series suggests atogepant as a possible prophylactic treatment for CH. Further research on CGRP signaling in CH and the implementation of well-designed clinical trials are necessary.

2024:  The effect of vitamin D supplementation on depression: a systematic review and dose–response meta-analysis of randomized controlled trials | Psychological Medicine | Cambridge Core

The impact of vitamin D supplementation on depressive symptoms remains uncertain. This study aimed to investigate the dose-dependent effects of vitamin D supplementation on depressive and anxiety symptoms in adults. We systematically searched PubMed, Scopus, and Web of Science up to December 2022 to identify randomized controlled trials evaluating the effects of vitamin D3 supplementation on depression and anxiety symptoms in adults. Using a random-effects model, we calculated the standardized mean difference (SMD) for each 1000 IU/day vitamin D3 supplementation. The GRADE tool assessed the certainty of evidence. Our analysis included 31 trials with 24189 participants. Each 1000 IU/day vitamin D3 supplementation slightly reduced depressive symptoms in individuals with and without depression (SMD: −0.32, 95% CI −0.43 to −0.22; GEADE = moderate). The effect was more pronounced in those with depressive symptoms (SMD: −0.57, 95% CI −0.69 to −0.44; n = 15). The greatest reduction occurred at 8000 IU/day (SMD: −2.04, 95% CI −3.77 to −0.31). Trials with follow-up ⩽8 weeks (SMD: −0.45, 95% CI −0.70 to −0.20; n = 8) and 8 to ⩽24 weeks (SMD: −0.47, 95% CI −0.70 to −0.24; n = 15) showed stronger effects compared to those lasting 24 to ⩽52 weeks (SMD: −0.13, 95% CI −0.28 to 0.02; n = 5) or longer than 52 weeks (SMD: 0.14, 95% CI −0.16 to 0.44; n = 3) (p group difference <0.001). Vitamin D3 supplementation had no significant effects on anxiety symptoms. In summary, this study suggests that vitamin D3 supplementation may effectively reduce depressive symptoms in short term. Further high-quality trials are warranted for a conclusive assessment of its impact on anxiety.

2025: https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2025.1622796/full

Our findings indicate that vitamin D supplementation is associated with a moderate but statistically significant improvement in depressive symptoms..... This meta-analysis demonstrates that vitamin D supplementation significantly alleviates depressive symptoms (SMD = -0.36), particularly in subgroups with baseline deficiency (<20 ng/mL) and comorbid chronic inflammatory conditions.

Faraidoon Haghdoost, Dilara Bahceci, Candice Delcourt, Tissa Wijeratne, Rigmor H Jensen, Carl Cincinnato, Susan Tomlinson, Bob Wold, Vince Polito, Cheryl Carcel, Usman Ashraf, Bronwyn Jenkins, Anja Sofie Petersen, Jason C Ray, Emmanuelle A D Schindler, Benjamin Tsang, Chris Gianacas, Anthony Rodgers

Published in Headache on January 21, 2026
Link: https://doi.org/10.1111/head.70031

Abstract:
Objective: This study was undertaken to identify gaps in cluster headache management, highlight patient-prioritized research needs, and assess patient interest in, and preferences for, clinical trial participation.

Published in Cephalalgia on January 2026
Link: https://doi.org/10.1177/03331024251411870

Abstract:
Cluster headache remains enigmatic with a significant unmet treatment need, especially in the chronic form. The steps made in 2025 have taken us further along the road to a true understanding of the still unknown pathophysiology, hopefully leading to a causal treatment.

Objectives.—To document the relationship between the use of subcutaneous (SQ) sumatriptan (sum) and a change in frequency pattern of cluster headache (CH) in six patients. To discuss the clinical and pathophysiological implications of this observation in the context of available literature.

Background.—Treatment with SQ sum may cause an increase in attack frequency of CH but data from literature are scant and controversial.

Methods.—Six CH sum-naïve patients (three episodic and three chronic according to the International Headache Society (IHS) criteria) are described.

Results.—All six patients had very fast relief from pain and accompanying symptoms from the drug but they developed an increase in attack frequency soon after using SQ sum. In all patients, the CH returned to its usual frequency within a few days after SQ sum was withdrawn or replaced with other drugs. Five patients were not taking any prophylactic treatment and SQ sum was the only drug prescribed to treat their headache.

Conclusions.—Physicians should recognize the possibility that treatment of CH with SQ sum may be associated with an increased frequency of headache attacks.

http://onlinelibrary.wiley.com/doi/10.1111/j.1526-4610.2004.04132.x/abstract

Published in Journal of Pain Research on January 8, 2026
Link: https://doi.org/10.2147/JPR.S550160

Abstract:
Cluster headache (CH) is a rare but highly disabling primary headache disorder characterized by severe unilateral attacks and autonomic symptoms. The metabolic mechanisms underlying CH remain poorly understood.
To investigate the potential causal effects of cerebrospinal fluid (CSF) metabolite levels on CH risk, and to explore possible reverse causal effects of CH on CSF metabolites, using a bidirectional Mendelian randomization (MR) approach.
We performed a bidirectional two-sample Mendelian randomization (MR) analysis integrating genome-wide association study (GWAS) data for 338 cerebrospinal fluid (CSF) metabolites and CH (1,833 cases and 498,515 controls from FinnGen release 12). Genetic instruments were selected at P < 1×10−5 (LD r2 < 0.01). The primary causal estimates were derived using the inverse-variance weighted (IVW) method under a random-effects model, complemented by MR-Egger, weighted median, and MR-PRESSO sensitivity tests. Multiple testing correction was performed using both Bonferroni and false discovery rate (FDR) approaches.
In the forward MR analysis, 11 CSF metabolites were significantly associated with CH risk (P<0.05). The strongest associations were observed for orotate (β = 0.53, 95% CI: 0.23–0.82, P = 0.0006), betaine (β = 0.47, 95% CI: 0.16–0.79, P = 0.0035), and 5-oxoproline (β = 0.57, 95% CI: 0.17–0.97, P = 0.0053). In the reverse MR analysis, eight metabolites, including lysine (β = 0.015, P = 0.029) and kynurenine (β = 0.025, P = 0.020), were nominally associated with genetic liability to CH. Sensitivity analyses showed no evidence of directional pleiotropy or heterogeneity (all P > 0.05).
This bidirectional MR study provides the first genetic evidence linking central metabolic alterations to CH susceptibility. While these results highlight potential metabolic biomarkers and mechanistic pathways, the findings remain preliminary due to modest statistical power and should be replicated in larger and ethnically diverse cohorts.

Published in Research Journal of Pharmacy and Technology on December 1, 2025
Link: https://doi.org/10.52711/0974-360X.2025.00887

Abstract:
Cluster headaches (CH) represent a debilitating neurological disorder characterized by severe, recurrent attacks of pain, often leading to significant impairment in quality of life. Traditional treatments often face issues like delayed onset of action, systemic side effects, and challenges in achieving optimal drug concentrations at the target site. Intranasal drug delivery has emerged as a promising alternative for the management of cluster headaches due to its potential for rapid absorption and direct access to the central nervous system. Among the novel strategies under investigation, cubosome-based nanocarriers have gained significant attention due to their unique structural properties, biocompatibility, and ability to encapsulate a wide range of therapeutic agents. This review highlights recent advancements in intranasal delivery systems, focusing on cubosome-based nanocarriers for the treatment of cluster headaches. It explores the physicochemical characteristics of cubosomes that make them ideal for intranasal administration, including their high surface area, mucoadhesive properties, and ability to enhance drug stability and bioavailability. The review also examines the potential of cubosome-encapsulated verapamil, a calcium channel blocker, as a promising candidate for rapid and effective cluster headache relief. Furthermore, it addresses the challenges and future perspectives in the development and clinical translation of cubosome-based intranasal therapies. By synthesizing current research findings, this review aims to provide insights into the potential of cubosome-based nanocarriers as a transformative approach in the treatment of cluster headaches, paving the way for more effective, patient-friendly therapeutic options.

Emmanuelle A D Schindler, Christopher H Gottschalk, Brian P Pittman, Deepak C D'Souza

Published in Headache on December 29, 2025
Link: https://headachejournal.onlinelibrary.wiley.com/doi/10.1111/head.70024

Abstract:
Objective: The goals of this study were to examine the therapeutic effects and safety of psilocybin given as a pulsed regimen for the prevention of migraine and to consider the blinding integrity of an active control agent.

Background: The administration of a single low dose of psilocybin was observed to have lasting therapeutic effects in one small pilot trial in migraine, although the ability of a pulse dose regimen, as practiced by patients with cluster headache, to potentially improve magnitude and/or duration of transitional preventive effects has not been studied. Furthermore, comparison to an active placebo agent that adequately mimics the acute subjective effects of psilocybin is required to improve blinding integrity and measure placebo effects.

Methods: In an exploratory randomized, double-blind, placebo-controlled, parallel group study, adults with migraine having at least two weekly migraine days at baseline (n = 18) participated in two drug administration sessions separated by 7 days during which they received zero, one, or two doses of psilocybin (10 mg; psi). Whenever participants did not receive psilocybin, they received diphenhydramine (25 mg; diph). Participant recruitment took place between September 2021 and August 2023. The primary outcome measure was a change in migraine frequency using headache diary data collected starting 2 weeks before and continuing through 8 weeks after the second drug session.

Results: In the 2 weeks after completion of the two drug administration sessions, the change from baseline in migraine days/week was not significantly different among groups [diph-diph: -0.7 (95% confidence interval, -1.5 to 0.2); diph-psi: -2.0 (-3.0 to -1.0); psi-psi: -1.7 (-4.1 to 0.7); Χ2 (2) = 4.56, p = 0.102], despite large effect sizes against the placebo group in the those receiving one (diph-psi; d = 1.66) or two (psi-psi; d = 0.69) doses of psilocybin. Similar reductions in migraine frequency approximating 50% were seen in all groups over the 8 weeks measured. The difference in 50% response rate among groups over 2 weeks, however, approached significance (diph-diph: 17%; diph-psi: 80%; psi-psi: 80%; p = 0.087). Drug confidence ratings (i.e., blinding integrity) suggested that diphenhydramine partially substituted for the acute effects of psilocybin. No correlations were observed between changes in migraine frequency after psilocybin and drug confidence, acute general drug effects, or acute psychedelic effects. No serious or unexpected adverse events occurred.

Conclusion: This exploratory study found similar reductions in migraine frequency with single-dose psilocybin, a two-dose pulse of psilocybin, or diphenhydramine placebo. Whereas blinding was incomplete in this study, this important topic is highlighted in the study design and findings. The potential for psilocybin to serve as a transitional treatment in migraine remains but will require careful planning in future studies to separate drug and non-drug effects. Furthermore, the inclusion of headache specialists in the design and execution of these future studies is necessary to preserve the viability of psilocybin treatment in headache medicine.

and nowadays everybody seems to be forgotten that it was like that. 
mind blown!

There is also a survey on Faraidoon's page assessing the cluster headache research gaps based on the patients perspectives.

https://www.faraidoonhaghdoost.com/post/cluster-headache-trial-got-funded-in-australia

https://www.georgeinstitute.org/news-and-media/news/hope-for-cluster-headache-community-as-psilocybin-trial-funded 

Juan Carlos Mario Andreani, Fabián Piedimonte, Osvaldo Bruera, Marco Lisicki, Diego Bashkansky

Published Vol. 19 in NeuroTarget 2025
Link: https://doi.org/10.47924/neurotarget2025549

Abstract:
Cluster headache (CH) is an extremely debilitating and often difficult-to-treat headache disorder characterized by recurrent attacks of excruciating pain associated with cranial autonomic symptoms. Several invasive neuromodulation procedures have been evaluated in the past, but the combination of these procedures to maximize response has not been studied in groups of patients. This presentation aims to describe an update on the evolution of cases based on a recent publication of ours.

This single-center, retrospective, observational study included seven patients (3F/4M) suffering from CCH, according to the diagnostic criteria of the current International Classification of Headache Disorders, and considered refractory based on the Consensus Statement of the European Headache Federation. Between February 2010 and March 2021, these patients underwent implantation of electrodes for SPG and greater occipital nerve (GON) stimulation ipsilateral to the side of the pain. The mean follow-up time was 6.38 years ± 3.6. Six out of the seven patients (86%) experienced good-to-excellent initial pain relief, defined as ≥50% reduction in VAS scores compared to baseline, with marked improvement in attack severity and functional impact. Almost complete remission of symptoms was achieved in most cases.

Multiple techniques have been proposed to control CH symptoms. Here we report, for the first time, that combined invasive SPG and GON neurostimulation significantly and enduringly improves CCH symptoms in a series of refractory patients. The relatively low number and severity of complications suggest a favorable risk-benefit profile.

Synergistic invasive SPG-GON stimulation appears to be a relatively safe and promising alternative for effective and long-lasting control of CCH.

Published in The Journal of Headache and Pain on November 25, 2025
Link: https://doi.org/10.1186/s10194-025-02209-7

Abstract:
Restlessness or agitation is one of the core symptoms of cluster headache (CH). However, the neurological substrate underlying this phenomenon has not been thoroughly analyzed. Whether they are attributed to the core aggression circuit or other CH-related structures remains unclear. The aim of this study is to use functional neuroimaging to elucidate the underlying mechanism of restlessness or agitation in CH.

We prospectively recruited consecutive patients with CH from the Headache Clinic of Taipei Veterans General Hospital between Jan 2022 and July 2025. Patients who consistently reported either the presence or absence of restlessness during CH attacks were enrolled and categorized into two groups: restlessness and non-restlessness. All enrolled patients underwent a functional magnetic resonance imaging (fMRI) scan. In the restlessness group, patients were required to exhibit restlessness during the fMRI scan, whereas those in the non-restlessness group showed no restlessness at the time of scanning. In this study, 32 regions of interest (ROIs) relevant to CH pathophysiology and the core aggression circuit were selected. To identify restlessness-related networks, ROI-to-ROI functional connectivity was compared between the restlessness and non-restlessness groups. To investigate downstream network for restlessness, ROI-to-voxel analyses were conducted using a general linear model, with ROIs showing significant differences in the initial ROI-to-ROI analysis as seeds. Multiple comparisons were corrected using both the false discovery rate (FDR) and family-wise error (FWE) methods.

A total of 24 patients with CH were recruited and categorized into two groups: restlessness (N = 14) and non-restlessness (N = 10). The ROI-to-ROI functional connectivity analysis of CH patients with restlessness revealed a significant connection between the non-pain side locus coeruleus (LC) and the pain-side substantia nigra pars compacta (SNpc), which survived FDR correction (p-FDR = 0.016). Seed-based general linear model analysis further revealed decreased connectivity between the pain-side SNpc and pain-side superior frontal gyrus, which survived FWE correction (p = 0.037). However, there were no significant cortical connectivity from the LC survived the FDR correction.

Our fMRI findings suggest that the neurological substrates of restlessness in CH involve the LC and SNpc rather than the core aggression network. Weakened connectivity from the SNpc to the superior frontal cortex may represent the downstream pathway contributing to restlessness in CH.

The first is Harzing’s Publish or Perish. It is a free citation analysis program that lets you easily search scientific literature across a range of journal sources. Link: https://harzing.com/resources/publish-or-perish

The second that I am really loving at the moment is Google’s NotebookLM. It allows you to upload papers, PDFs, and links, then ask structured questions and generate summaries, comparisons and notes directly from your sources. For anyone trying to understand mechanisms, track themes across papers or just stay organised while reading, it is extremely handy. Link: https://notebooklm.google

Both tools make it easier for patients who like to follow the science closely to evaluate studies and stay on top of emerging research. If anyone wants a quick explanation of how to use either tool for cluster headache-related topics, I am happy to share examples.

The last tool - bonus lol, I went looking for something to match CHFathers cat picture in a recent AI post - found another Google tool. An experimental tool for visual exploration: you input images for subject, scene, style and the system remixes them into new visuals - here's what I got for my new CH Forums profile pic - I am here to stay now! https://labs.google/fx/tools/whisk

Published in Annals of Indian Academy of Neurology on November 12, 2025
Link: https://doi.org/10.4103/aian.aian_417_25

Abstract:
Background and Objectives:
Migraine is a debilitating neurological disorder affecting 10%–20% of the global population, with significant socioeconomic burdens. Vitamin D deficiency, prevalent in over 1 billion individuals, has been proposed as a modifiable risk factor in migraine management due to its potential role in pain modulation and neuroinflammation. This scoping review aimed to map global vitamin D deficiency prevalence across migraine subtypes and geographic regions, synthesize clinical correlations between vitamin D status and migraine characteristics, and explore heterogeneity in therapeutic evidence across paediatric, chronic, and refractory migraine subgroups.

Methods:
A systematic search of PubMed, Scopus, and Embase was conducted, identifying 3,447 records initially. After screening and eligibility assessment, 30 studies were included. These encompassed observational studies (n = 14), randomized controlled trials (n = 9), and systematic reviews (n = 7). Data were synthesized narratively due to clinical heterogeneity and the predominance of cross sectional evidence.

Results:
Vitamin D deficiency (serum 25 hydroxyvitamin D [25(OH) D] <20 ng/mL) was highly prevalent among migraine patients (65%–88%), particularly in chronic migraine (80%–92%) and high latitude populations (>40°N: 75%–90%). Inverse correlations were observed between vitamin D levels and headache frequency and disability scores. High dose vitamin D supplementation (≥50,000 IU/week) reduced migraine attacks by 50%–72% in deficient adults, while minimal benefit was seen in replete individuals. Single trials revealed enhanced efficacy when combined with probiotics or topiramate in refractory and paediatric cases, respectively, but this requires further validation.

Conclusion:
Vitamin D deficiency is consistently associated with increased migraine burden. Supplementation shows context dependent efficacy, particularly in deficient individuals and specific subgroups. Future research should focus on mechanistic trials, global standardization of assays, and comprehensive outcome assessments. Clinically, baseline 25(OH)D testing is recommended to guide targeted supplementation strategies.

Published in IP Indian Journal of Clinical and Experimental Dermatology on 26 September 2025
Link: https://doi.org/10.18231/j.ijced.89447.1758864688

Abstract:
Background: Autoimmune disorders, particularly psoriasis, are often associated with vitamin D deficiency and vitamin D resistance. Higher daily doses of vitamin D3 are considered effective in overcoming vitamin D resistance and reversing psoriasis symptoms. This study was conducted to evaluate the safety and efficacy of individualized, prolonged high‑dose daily oral vitamin D3 therapy in patients with moderate‑to‑severe psoriasis.
Materials and Methods: In this study, we present data from 95 patients with moderate‑to‑severe psoriasis who underwent individualized high‑dose daily oral vitamin D3 (cholecalciferol) therapy. From this cohort, six representative cases are described in detail to illustrate the approach to personalized dosing and the monitoring process using biochemical markers such as parathyroid hormone (PTH) and ionized calcium. The efficacy of the intervention was assessed using Psoriasis Area and Severity Index (PASI) scores, while safety was evaluated through regular monitoring of serum creatinine and ionized calcium levels. Statistical analyses were conducted to examine the relationship between vitamin D3 dosage, serum 25(OH)D levels, PTH suppression, and clinical improvement.
Results: Significant clinical improvement or remission was noted, without hypercalcemia or toxicity. PTH levels consistently declined in parallel with clinical response, suggesting vitamin D action.
Conclusion: Monitored oral vitamin D3 therapy in higher than supplemental dose, can be a safe and effective treatment for psoriasis.

Published in International Journal of Neuroscience on October 30, 2025
Link: https://doi.org/10.1080/00207454.2025.2580332

Abstract:
This study employs the Mendelian randomization (MR) approach to investigate the causal relationships among immune cells, cluster headache (CH), and potential mediation by serum metabolites. Using genome-wide association study (GWAS) data, MR analyses were conducted on 731 immune cell phenotypes, 1400 serum metabolites, and CH. The inverse variance weighted (IVW) method was employed as the primary analytical approach, supplemented by MR-Egger and weighted median analyses. Stability of results was assessed using Cochran’s Q and other statistical tests.
The analysis identified a negative causal relationship between CD39+ CD4+ %T cells and CH, supported by sensitivity analyses. Reverse MR analysis showed no effect of CH on CD39+ CD4+ T cells, suggesting a unidirectional role of these cells in reducing CH risk. Further mediation MR analysis indicated that CD39+ CD4+ T cells may influence CH risk through the regulation of either the adenosine 5′-diphosphate (ADP) to N-acetylneuraminate ratio or the choline phosphate to phosphoethanolamine ratio, with mediation effect ratios of 12.4% and 12.5%, respectively.
CD39+ CD4+ T cells may reduce CH risk by increasing the adenosine 5′-diphosphate (ADP) to N-acetylneuraminate ratio or the choline phosphate to phosphoethanolamine ratio. These findings provide novel insights into potential targets for the prevention and treatment of CH.

Published by University of East Anglia on October 30, 2025
Link: https://ueaeprints.uea.ac.uk/id/eprint/100852

Abstract:
Cluster Headache (CH) is cited as one of the most painful experiences known to humankind. This thesis portfolio aimed to provide a greater insight into the psychological aspects of CH. A systematic review accumulated evidence of rates of depression and suicidality in individuals living with CH and an empirical paper explored the psychological experience of living with CH.

A systematic review and meta-analysis was conducted to determine rates of depression and suicidality amongst individuals with CH compared to non-headache controls and individuals with other primary headache conditions (Migraine or Tension-Type Headache (TTH)). Secondly, 13 interviews were conducted with individuals living with CH and this data was analysed using Reflexive Thematic Analysis.

Meta-analyses of 20 studies showed that compared to non-headache controls, adults with CH had much higher levels of depression and suicidality. However, there was no significant difference in depression levels between CH and Migraine individuals. Comparing individuals with CH and TTH, the initial meta-analysis found no significant difference in depression levels, but a sensitivity analysis showed TTH individuals having higher levels of depression. Considerable heterogeneity and publication bias were present. Reflective Thematic Analysis identified five themes relevant to the CH experience: “Darkness”, “Battling”, “Shifting”, “Control”, and “Despair”. There were differences within these themes based on whether a person was in the moment of pain or between attacks, whether they had the chronic or episodic form of CH, and how long they had lived with CH.

This portfolio highlighted that psychological aspects of CH include increased depression and suicidality. Increased depression was also present for the other primary headache disorders. The empirical paper identified various psychological processes important in the experience of CH which could be the target of psychological treatment.

Published in Pain Practice on October 6, 2025
Link: https://doi.org/10.1111/papr.70084

Abstract:
Cluster headache (CH) is a rare but severe primary headache disorder characterized by recurrent attacks of unilateral, typically periocular pain lasting 15 min to 3 h, accompanied by ipsilateral autonomic symptoms and restlessness or agitation. Attacks may occur multiple times daily and present in clusters lasting weeks to months, interspersed with remission periods in episodic CH, or without remission in chronic CH.
This review summarizes the clinical evidence supporting the use of transcutaneous cervical vagus nerve stimulation (tcVNS) for both the acute and preventive treatment of CH. Relevant clinical trials, real-world studies, and guideline recommendations are discussed.
Pharmacological therapy for CH includes triptans and high-flow oxygen for acute management, and verapamil, corticosteroids, or galcanezumab for prevention. For patients with inadequate response or intolerance to these options, neuromodulation may be required. TcVNS has emerged as a noninvasive, safe, and effective alternative to invasive neuromodulation. Clinical trials have demonstrated significant reductions in attack frequency and intensity, leading to U.S. Food and Drug Administration (FDA) clearance and UK National Institute for Health and Care Excellence (NICE) approval for both acute and preventive treatment of CH.
TcVNS represents a well-tolerated, noninvasive neuromodulatory option for patients with cluster headache, offering both acute and preventive benefits. This paper provides an overview of the current evidence, mechanisms of action, and practical guidelines for incorporating tcVNS into clinical management.

Published in European Journal of Neurology on September 26, 2025
Link: https://doi.org/10.1111/ene.70341

Abstract: (partial selection)

This large-scale study demonstrated increased PACAP-38 levels in all disease states of cluster headache compared to headache-free controls, strengthening the hope of a possible effect of PACAP-38 targeting treatments in future trials. The lacking correlation between PACAP-38 and CGRP levels should be interpreted with caution and needs to be investigated in future studies.

https://journals.sagepub.com/doi/10.1177/25158163251345472?fbclid=IwY2xjawL5Bk9leHRuA2FlbQIxMABicmlkETFVSjB2bTBMbDVySHZHekZQAR7JbiuavTIRoFm_QyX7lPPsBVEVT64RWoUx-vPIuc8Q34U2o6tJrlcN-cwJHQ_aem_BzEAWxqD5Ysi1yk8bnko4Q

Abstract

Background

Methods

Results

Conclusion

They found a significant decrease in Heart Rate Variability (HRV) in CH patients compared to controls, this lower HRV  suggesting a sympathetic predominance / reduced parasympathetic activity.

CH patients also had a higher mean heart rate and significantly higher plasma norepinephrine levels both when lying down and standing which indicates increased sympathetic activity.

This study suggests an ANS imbalance in CH  even during remission pointing to a decrease in parasympathetic activity and sympathetic hyperactivity. They call for more research. 

This also makes me consider the value of, I believe the term is non invasive vagus nerve stimulators via devices like the Gammacore and others like the Pulsetto. The latter being fairly affordable although requires a level of consistent daily use to see the benefit it promotes, one of which was an increase in HRV. Full disclosure, I have a Pulsetto but being in remission and busy I don’t use it frequently enough to offer any meaningful feedback other than to say the sensation is funky at first but you get used to it. 

You can find the full preprint here: 

https://www.researchsquare.com/article/rs-6871540/v1

It got me thinking. Has there been any research on Cluster Headaches as a symptom of some kind of virus or infection that perhaps makes it's way to the brain/hypothalamus?  

I did some googling and searching on this site, but I don't see many theories of this kind. I see @didgens started a topic anout ear infections (which I suffered from as a child as well!). Curious if any research had been done on CH being on-set as a symptom, or caused by, something else? I always sort of defulted to the thought that I was born with this, but perhaps we all picked this up somewhere along the way? 

https://www.npr.org/sections/thesalt/2018/06/25/621080751/red-meat-allergies-caused-by-tick-bites-are-on-the-rise